Department of Genetics, Faculty of Agriculture, Alexandria University, Alexandria, Egypt.
Department of Nucleic Acid Research, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications, Alexandria, Egypt.
BMC Cancer. 2024 Aug 8;24(1):971. doi: 10.1186/s12885-024-12683-y.
Urinary bladder cancer, is the 10th most common global cancer, diagnosed in over 600,000 people causing 200,000 deaths annually. Artemisinin and its derivatives are safe compounds that have recently been proven to possess potent anti-tumor effects in vivo, through inhibition of cancer cell growth. The aim of this study is to assess the efficiency of artemisinin as a cancer treatment alone and as a pre-treatment fore cisplatin therapy for high grade urothelial carcinoma.
Sixty male albino mice were divided into six groups, and BBN was used to induce urinary bladder cancer. Blood samples were tested for renal functions and complete blood counts, kidney and urinary bladder tissues were harvested for histopathological examination. Total RNAs from urinary bladder tissues was collected, and gene expression of FGFR3, HRAS, P53, and KDM6A was quantified using qRT-PCR.
Compared to the induced cancer group, the results revealed that FGFR3 expression levels were down-regulated in the induced cancer group treated by artemisinin only and the induced cancer group pre-treated with artemisinin prior to cisplatin by ~ 0.86-fold and 0.4-folds, respectively, aligning with HRAS down-regulation by ~ 9.54-fold and 9.05-fold, respectively. Whereas, P53 expression levels were up-regulated by ~ 0.68-fold and 0.84-fold, respectively, in parallel with KDM6A expression, which is up-regulated by ~ 0.95-folds and 5.27-folds, respectively. Also, serum creatinine and urea levels decreased significantly in the induced cancer group treated by artemisinin alone and the induced cancer group pre-treated with artemisinin prior to cisplatin, whereas the induced cancer group treated by cisplatin their levels increased significantly. Moreover, Hb, PLT, RBC, and WBC counts improved in both cancer groups treated by artemisinin alone and pre-treated with artemisinin prior to cisplatin. Histologically, in kidney tissues, artemisinin pre-treatment significantly reduced renal injury caused by cisplatin. While Artemisinin treatment for cancer in bladder tissues reverted invasive urothelial carcinoma to moderate urothelial dysplasia.
This study indicates that artemisinin demonstrated a significant effect in reversal of the multi-step carcinogenesis process of high grade urothelial carcinoma and could enhance the effect of cisplatin therapy using artemisinin pre-treatment.
膀胱癌是全球第 10 大常见癌症，每年诊断出超过 60 万人，导致 20 万人死亡。青蒿素及其衍生物是安全的化合物，最近已被证明具有抑制癌细胞生长的体内抗肿瘤作用。本研究旨在评估青蒿素单独作为癌症治疗以及作为顺铂治疗高级尿路上皮癌的预处理的效率。
将 60 只雄性白化小鼠分为 6 组，使用 BBN 诱导膀胱癌。检测血液样本的肾功能和全血细胞计数，采集肾脏和膀胱组织进行组织病理学检查。收集膀胱组织的总 RNA，使用 qRT-PCR 定量 FGFR3、HRAS、P53 和 KDM6A 的基因表达。
与诱导的癌症组相比，结果显示仅用青蒿素治疗的诱导癌症组和先用青蒿素预处理然后用顺铂治疗的诱导癌症组中 FGFR3 的表达水平分别下调了0.86 倍和 0.4 倍，与 HRAS 的下调一致分别为9.54 倍和 9.05 倍。而 P53 的表达水平分别上调了0.68 倍和 0.84 倍，与 KDM6A 的表达平行上调了0.95 倍和 5.27 倍。此外，仅用青蒿素治疗的诱导癌症组和先用青蒿素预处理然后用顺铂治疗的诱导癌症组的血清肌酐和尿素水平显著降低，而仅用顺铂治疗的诱导癌症组其水平显著升高。此外，两种用青蒿素单独治疗和用青蒿素预处理然后用顺铂治疗的诱导癌症组的 Hb、PLT、RBC 和 WBC 计数均有所改善。组织学上，在肾脏组织中，青蒿素预处理显著减轻了顺铂引起的肾损伤。而青蒿素治疗膀胱组织中的癌症使侵袭性尿路上皮癌逆转至中度尿路上皮发育不良。
本研究表明，青蒿素在逆转高级尿路上皮癌的多步癌变过程中表现出显著的效果，并可以通过青蒿素预处理增强顺铂治疗的效果。
